To investigate the effects of genetic and environmental factors, and their interactions, on respiratory health in adults we have established several high-quality population resources. We have been working with the extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study to examine both genetic and environmental factors in adult respiratory health. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We added the assessment of exposure to traffic to this dataset and have examined this surrogate of traffic related air pollution in relation to respiratory and cardiovascular endpoints. In the past year we have published on the relationship between traffic related air pollution and venous thromboembolic disease in ARIC. We have used the genome wide association genotyping in ARIC to look for novel genes associated with pulmonary function and chronic obstructive pulmonary disease (COPD). We formed a pulmonary function analysis group within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology) which includes several other cohorts with genome wide association genotyping and pulmonary function data. In our CHARGE meta-analysis, we identified eight novel loci related to pulmonary function. All but one have now been replicated by other groups. We are participating in an extramurally funded project to use next generation sequencing to narrow down the causal SNPs involved in the associations that we have identified from GWAS. In the past year we have collaborated with a European consortium called SpiroMeta to do large meta-analyses. In a meta-analysis of the same pulmonary function traits we have identified an additional 16 novel loci. We are completing a manuscript on meta-analysis of COPD in CHARGE and SpiroMeta. We are also examining genome-wide interactions with smoking in relation to pulmonary function. This work lead to a collaborative methods paper with extramural investigators. We are also working on longitudinal analysis of pulmonary function which has involved application of novel methods in the GWAS setting. We also also working with a consortium called CARe for examination of the GWAS data from African-Americans in ARIC and other cohorts. Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We continued to expand these observations in new papers this year. To follow-up on these observations, we are doing a new study which is described in a separate annual report - ES102385-01. Another population is the NIEHS Sister Study. This NIEHS cohort has enrolled 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is being followed up annually. In collaboration with investigators at the EPA-UNC Human Exposure Facility, I have established a study to follow-up on recent experimental work showing that obese mice have greater respiratory response to ozone than lean mice. This work also follows up our recent finding that subjects with higher BMI have greater drop in pulmonary function (FEV1) in response to acute ozone exposure(Bennett et al., Inhalation Toxicology, 2007). We have established an experimental study where we expose centrally obese and lean women to ozone and measure spirometry, air resistance, airway hyperresonsiveness and inflammatory responses to the exposure. Enrollment is nearly complete for this study.